Our studies have revealed that Toxoplasma gondii confers upon mice remarkable resistance against a variety of unrelated pathogenic organisms including bacteria, fungi and viruses. Further studies showed that the "broad spectrum" resistance conferred by T. gondii also extends to tumor development. Toxoplasma and a related protozoan, Besnoitia jellisoni conferred significant resistance to development of autochthonous tumors (AKR leukemia and mammary carcinoma in C3H mice), and transplantable tumors (L-1210 leukemia, Sarcoma 180 and Friend leukemia). The underlying mechanism of resistance against both infection and tumor development in Toxoplasma- and Besnoitia-infected mice appeared to be the activated macrophage. As Toxoplasma is a latent parasite in approximately 30-60% of the adult population in the United States, and since this infection persists for the entire life of an individual and maintains sufficient activity in human and animal hosts to provide a constant antigenic stimulus, the immunotherapeutic use of this organism or its antigens in prevention or treatment of human cancer might be considered if further promising data in animals are made available. We propose to obtain such data through an in-depth study of Toxoplasma as an agent for both prevention and therapy of cancer and to evaluate various strains and antigens of this organism in a variety of animal-tumor models. We have a large number of strains of Toxoplasma which readily establish a chronic infection in animals similar to that observed in man. We propose to compare these strains as to their efficacy in prevention of development of tumors and treatment of already established tumors, and to administer Toxoplasma antigens, both living and killed, to enhance resistance against already established tumors in laboratory animals with chronic Toxoplasma infection. This approach to prevention and treatment of tumors will then be assessed in combination with established alternative therapeutic measures such as chemotherapy and radiotherapy.